The proposed research on the pathogenesis of obstructive sleep apnea (OSA) is based on the theory that upper airway closures during sleep result from an imbalance between two counteracting forces: the dilating force created by inspiratory activation of upper airway muscles and the narrowing force generated by intraluminal subatmospheric inspiratory pressure. An opposing theory suggests that upper airway muscles physically active on expiration play an important role in the pathogenesis of upper airway closures during sleep. To test this theory, the activity of three such muscles: the superior pharyngeal constrictor, thyroarytenoid and interarytenoideus will be measured in OSA subjects at different levels of CO2 and O2 during wakefulness and with and without nasal airway positive pressure (NAPP) during sleep. alternatively, the neural activation of upper airway muscles with phasic inspiratory activity may be abnormally decreased in OSA subjects. To examine this possibility, alae nasi, genioglossus and posterior cricoarytenoid responses to 1) hypercapnia and hypoxia during wakefulness and 2) changes in positive airway pressure during sleep will be determined in OSA subjects prior to and one month following home treatment with NAPP. The increase in subatmospheric upper airway pressure and withdrawal of phasic volume feedback associated with inspiratory efforts during upper airway occlusion cause a reflex activation of upper airway muscles in many animal preparations. Our recent study on the genioglossus muscle suggests a blunting of this reflex in sleeping adults which could predispose to upper airway closures. Experiments will be performed in normal adult subjects to determine the response of other upper airway muscles to intermittent upper airway occlusion during sleep. The progressive increase in upper airway muscle activity during an apneic episode in man is associated with an increase in chemical drive and subatmospheric upper airway pressure. Experiments will be performed in decerebrate cats to determine the effect of chemical drive, upper airway receptors and also brainstem lesions on suppression of upper airway motoneuron activity by phasic volume feedback.